Fbxl19 recruits Rnf20 to CpG Islands and promotes H2B mono-ubiquitination [Affymetrix]. Mus musculus

Rnf20 catalyzes lysine 120 mono-ubiquitination of histone H2B (H2Bub1) that has been previously involved in normal differentiation of embryonic stem (ES) and adult stem cells. However, the mechanisms underlying by which Rnf20 is recruited to its target chromosomal loci to generate H2Bub1 are still elusive. Here, we reveal that Fbxl19, a CxxC domain-containing protein, physically interacts with Rnf20, guides it preferentially to CpG island-containing target promoters, and thereby promotes mono-ubiqutination of H2B. We first show that up-regulation of Fbxl19 induces the level of global H2Bub1, while down-regulation of Fbxl19 reduces the level of H2Bub1 in mouse ES cells. Our genome-wide target mapping unveils the preferential occupancy of Fbxl19 on CpG island-containing promoters, and we further show that the binding of Fbxl19 is essential for the recruitment of Rnf20 to its target genes and subsequent H2Bub1. Altogether, our results demonstrate that Fbxl19 plays critical roles in the H2Bub1 pathway by recruiting Rnf20 to CGI target genes specifically and selectively. Overall design: We investigated the roles of Fbxl19 in mouse embryonic stem (ES) cells by knocking down Fbxl19. Total RNAs were extracted from the ES cells upon KD of Fbxl19 and then hybridized on Affymetrix Mouse GeneChip 430A 2.0. We monitored global gene expression changes upon KD of Fbxl19